Cancer-Focused Research:

The main focus of my research program is to study breast and prostate cancer progression. Our starting point is a gene named MASPIN, a unique member of SERPIN family that plays roles in normal tissue development, tumor metastasis, and angiogenesis. Genetic studies by my laboratory using maspin transgenic and knockout mice demonstrated an important role of maspin in normal mammary, prostate, and embryonic development. Recently, we have identified several new properties of maspin. As a protein that is present on cell surface, maspin controls cell-ECM adhesion. We believe that this function is responsible for maspin-mediated suppression of tumor cell motility and invasion. We have also discovered that maspin is involved in the induction of tumor cell apoptosis through a mitochondrial death pathway. The long-term goals of our maspin project are to elucidate the molecular mechanism by which maspin controls cell adhesion and apoptosis, and to analyze the effect of maspin on mammary gland and other tissue development, and to study the effect of loss of maspin on early mammary lesions and late stage tumor progression. We believe that these analyses are not only important for basic biology and but also may lead to a therapy for cancer and other developmental diseases. In addition to the maspin project, my laboratory has also established mouse mammary tumor models to study the unique process of tumor metastasis in particular. For example, we have established a new mouse mammary tumor cell line, which spontaneously metastasizes to the bone upon inoculation to the mammary fat pads of BALB/c syngeneic mice. Comparison of gene expression profile between highly metastatic tumor cells and non-metastatic cells by Affymetrix microarray has identified a list of candidate genes, which might play roles in breast cancer bone metastasis. We have also used these animal models for gene therapy. These studies will likely open new directions for cancer treatment in the near future.